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King's College London - Health: More than a medical matter

Depression hits genetic switch to disrupt brain cells

20 August 2012

By Maren Urner

Appeared in BioNews 669

Researchers at Yale University in the USA may have found an explanation for why patients with severe depression often show decreased volume of certain areas of the brain.

Their study, published in the journal Nature Medicine, identified a genetic 'switch' - a transcription factor - which regulates several genes related to the communication between neurons. This transcription factor, called GATA1, appears to be overproduced in depressed patients, say the scientists.

Senior author Professor Ronald Duman said the team 'wanted to test the idea that stress causes a loss of brain synapses in humans'. Synapses are the interfaces where two or more brain cells communicate. He says the study shows that 'circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated'.

The researchers analysed post-mortem brain tissue of depressed and non-depressed people donated from a brain bank. They found lower expressions of several genes related to synaptic function, as well as fewer synapses, in a frontal region of the brain of depressed people. They also found that the transcriptional factor GATA1 was up-regulated in the depression group.

To test the relationship between GATA1 and brain volume, the scientists activated the transcription factor in the frontal brain region of rats. Doing so led to a decrease in expression of genes related to synapse function, causing the loss of connection points between neurons. Also, the rodents started to display depressive behaviour.

A link between the structural changes of the frontal brain region in depressed patients and biological mechanisms needs further corroboration. The Yale researchers believe the observed damage could be a result of chronic stress and hope that their findings will lead to new treatments against depression.

'We hope that by enhancing synaptic connections, either with novel medications or behavioural therapy, we can develop more effective antidepressant therapies', said Professor Duman.


Nature Medicine | 12 August 2012
Huffington Post | 13 August 2012
CBS News | 13 August 2012
Mail Online | 13 August 2012
EurekAlert! (press release) | 12 August 2012


18 November 2013 - by MarĂ­a Victoria Rivas Llanos 
Severe depression speeds up the ageing process of our cells, researchers have found... [Read More]
20 May 2013 - by Dr Amina Aitsi-Selmi 
Genes believed to regulate sleep rhythm are expressed abnormally in people with major depressive disorders, scientists say... [Read More]
03 December 2012 - by Maren Urner 
The risk of depression in adolescents exposed to negative environments during their childhood is partly dependent on their genetic make-up, suggest researchers... [Read More]
26 November 2012 - by Nicola Davis 
A gene linked to obesity may also provide protection from major depression, say scientists... [Read More]

23 May 2011 - by Dr Rosie Morley 
Scientists believe they have identified a new genetic link to severe depression.... [Read More]
28 February 2011 - by Owen Clark 
A new study has demonstrated that levels of a hormone involved in the response to stress could explain why some people develop post-traumatic stress disorder (PTSD). The research, conducted by scientists at Emory University and the University of Vermont in the US, studied a group of patients considered at high-risk of developing PTSD... [Read More]
14 February 2011 - by Dr Lux Fatimathas 
US researchers have found a correlation between levels of the brain chemical neuropeptide Y (NPY) and an individual's emotional wellbeing. Mutations in the NPY gene, leading to decreased levels of the molecule, correlated with a decreased ability to deal with stressful situations and an increased susceptibility to depression.... [Read More]
30 November 2009 - by Dr Rachael Panizzo 
Researchers at the University of Edinburgh, Scotland, have identified a gene that may be involved in mental illness and maintaining brain health. The scientists compared the genes of 2,000 psychiatric patients and 2,000 healthy people in Scotland. They discovered that the ABCA13 gene was faulty more frequently in patients with severe mental illness - such as schizophrenia, bipolar disorder and depression - than in the healthy control group.... [Read More]
22 June 2009 - by Dr Sarah Spain 
A new study published in the Journal of the American Medical Association has called into question a previously reported link between a gene variation and risk of depression. The study, funded by the National Institute of Mental Health (NIMH) and carried out by scientists from six US universities, was led by Dr Kathleen Merikangas from the NIMH Intramural Research program and Dr Neil Risch of the University of California, San Francisco.... [Read More]

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